Menstrual Blood-Derived Endometrial Stem Cells’ Impact for the Treatment Perspective of Female Infertility

When looking for the causes and treatments of infertility, much attention is paid to one of the reproductive tissues—the endometrium. Therefore, endometrial stem cells are an attractive target for infertility studies in women of unexplained origin. Menstrual blood stem cells (MenSCs) are morphologically and functionally similar to cells derived directly from the endometrium; with dual expression of mesenchymal and embryonic cell markers, they proliferate and regenerate better than bone marrow mesenchymal stem cells. In addition, menstrual blood stem cells are extracted in a non-invasive and painless manner. In our study, we analyzed the characteristics and the potential for decidualization of menstrual blood stem cells isolated from healthy volunteers and women diagnosed with infertility. We demonstrated that MenSCs express CD44, CD166, CD16, CD15, BMSC, CD56, CD13 and HLA-ABC surface markers, have proliferative properties, and after induction of menstrual stem cell differentiation into epithelial direction, expression of genes related to decidualization (PRL, ESR, IGFBP and FOXO1) and angiogenesis (HIF1, VEGFR2 and VEGFR3) increased. Additionally, the p53, p21, H3K27me3 and HyperAcH4 proteins’ expression increased during MenSCs decidualization, they secrete proteins that are involved in the regulation of the actin cytoskeleton, estrogen and relaxin signaling pathways and the management of inflammatory processes. Our findings reveal the potential use of MenSCs for the treatment of reproductive disorders.

Intrauterine transplantation of autologous menstrual blood stem cells in the treatment of refractory intrauterine adhesion: a prospective cohort study

Background: The loss of endometrial stem cells has been associated with intrauterine adhesion caused by miscarriage, repeated improper intrauterine operation or infection. Cell-based therapies are promising in regenerative medicine. However, the effects of menstrual blood stem cells (MenSCs) therapy on impaired endometrium need to be explored and validated. This study evaluates the effects of intrauterine transplantation of MenSCs on endometrial thickness and pregnancy outcomes in patients with refractory intrauterine adhesion. Methods: This study included a group of infertile women (n=12, age 22-40 years), with refractory intrauterine adhesion (Grade III – IV). Autologous MenSCs isolated from the women’ menstrual blood were expanded in vitro and transplanted into their uteruses, followed by hormone replacement therapy. Transvaginal ultrasound examination was performed to assess the endometrial thickness. Transabdominal ultrasound was conducted to detect pregnancy outcome. Results: Autologous MenSCs were successfully isolated and expanded from menstrual blood and transplanted into the uterus of each patient. A significant improvement of the endometrial thickness was observed (from 3.9±0.9 mm pre-treatment to 7.5±0.6 mm post-treatment (P<0.001)). No adverse reaction was observed. The duration of menstruation was increased (from 2.4±0.7 days pre-treatment to 5.3±0.6 days post-treatment (P<0.001)). Five out of 12 patients achieved clinical pregnancy. Conclusions: Intrauterine transplantation of autologous MenSCs results in regeneration of endometrium, a prolongation of menstrual duration and an increase rate of pregnancy in patients with refractory intrauterine adhesion.

The Potential of Menstrual Blood-Derived Mesenchymal Stem Cells for Cartilage Repair and Regeneration: Novel Aspects

Menstrual blood is a unique body fluid that contains mesenchymal stem cells (MSCs). These cells have attracted a great deal of attention due to their exceptional advantages including easy access and frequently accessible sample source and no need for complex ethical and surgical interventions, as compared to other tissues. Menstrual blood-derived MSCs possess all the major stem cell properties and even have a greater proliferation and differentiation potential as compared to bone marrow-derived MSCs, making them a perspective tool in a further clinical practice. Although the potential of menstrual blood stem cells to differentiate into a large variety of tissue cells has been studied in many studies, their chondrogenic properties have not been extensively explored and investigated. Articular cartilage is susceptible to traumas and degenerative diseases, such as osteoarthritis, and has poor self-regeneration capacity and therefore requires more effective therapeutic technique. MSCs seem promising candidates for cartilage regeneration; however, no clinically effective stem cell-based repair method has yet emerged. This chapter focuses on studies in the field of menstrual blood-derived MSCs and their chondrogenic differentiation potential and suitability for application in cartilage regeneration. Although a very limited number of studies have been made in this field thus far, these cells might emerge as an efficient and easily accessible source of multipotent cells for cartilage engineering and cell-based chondroprotective therapy.